Apparatus for subretinal administration of therapeutic agent via a curved needle

ABSTRACT

An apparatus includes a body, a cannula, and a needle. The cannula is flexible and extends distally from the body. The needle is slidably disposed in the cannula. The needle includes a sharp distal tip and a curved portion. The needle is configured to translate relative to the cannula between a proximal position and a distal position. The distal tip is configured to be positioned inside the cannula when the needle is in the proximal position. The distal tip is configured to be positioned outside the cannula when the needle is in the distal position. The needle is resiliently biased to extend along a curve through the curved portion.

PRIORITY

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/305,767, entitled “Curved Needle Choroidal Penetration,” filedMar. 9, 2016, the disclosure of which is incorporated by referenceherein.

BACKGROUND

The human eye comprises several layers. The white outer layer is thesclera, which surrounds the choroid layer. The retina is interior to thechoroid layer. The sclera contains collagen and elastic fiber, providingprotection to the choroid and retina. The choroid layer includesvasculature providing oxygen and nourishment to the retina. The retinacomprises light sensitive tissue, including rods and cones. The maculais located at the center of the retina at the back of the eye, generallycentered on an axis passing through the centers of the lens and corneaof the eye (i.e., the optic axis). The macula provides central vision,particularly through cone cells.

Macular degeneration is a medical condition that affects the macula,such that people suffering from macular degeneration may experience lostor degraded central vision while retaining some degree of peripheralvision. Macular degeneration may be caused by various factors such asage (also known as “AMD”) and genetics. Macular degeneration may occurin a “dry” (nonexudative) form, where cellular debris known as drusenaccumulates between the retina and the choroid, resulting in an area ofgeographic atrophy. Macular degeneration may also occur in a “wet”(exudative) form, where blood vessels grow up from the choroid behindthe retina. Even though people having macular degeneration may retainsome degree of peripheral vision, the loss of central vision may have asignificant negative impact on the quality of life. Moreover, thequality of the remaining peripheral vision may be degraded and in somecases may disappear as well. It may therefore be desirable to providetreatment for macular degeneration in order to prevent or reverse theloss of vision caused by macular degeneration. In some cases it may bedesirable to provide such treatment in a highly localized fashion, suchas by delivering a therapeutic substance in the subretinal layer (underthe neurosensory layer of the retina and above the retinal pigmentepithelium) directly adjacent to the area of geographic atrophy, nearthe macula. However, since the macula is at the back of the eye andunderneath the delicate layer of the retina, it may be difficult toaccess the macula in a practical fashion.

While a variety of surgical methods and instruments have been made andused to treat an eye, it is believed that no one prior to the inventorshas made or used the invention described in the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

While the specification concludes with claims which particularly pointout and distinctly claim this technology, it is believed this technologywill be better understood from the following description of certainexamples taken in conjunction with the accompanying drawings, in whichlike reference numerals identify the same elements and in which:

FIG. 1 depicts a perspective view of an exemplary instrument forsubretinal administration of a therapeutic agent from a suprachoroidalapproach;

FIG. 2 depicts a perspective view of the distal end of an exemplarycannula that may be incorporated into the instrument of FIG. 1;

FIG. 3A depicts a cross-sectional side view of the cannula of FIG. 2,with the cross-section taken along line 3-3 of FIG. 2, with a needle ina first longitudinal position;

FIG. 3B depicts a cross-sectional side view of the cannula of FIG. 2,with the cross-section taken along line 3-3 of FIG. 2, with the needlein a second longitudinal position;

FIG. 4A depicts a cross-sectional view of an eye of a patient, with achandelier installed in the eye;

FIG. 4B depicts a cross-sectional view of the eye of FIG. 4A, with asuture loop attached to the eye, and with a sclerotomy being performed;

FIG. 4C depicts a cross-sectional view of the eye of FIG. 4A, with theinstrument of FIG. 1 being inserted through the sclerotomy opening andin between the sclera and choroid of the eye;

FIG. 4D depicts a cross-sectional view of the eye of FIG. 4A, with theinstrument of FIG. 1 under direct visualization at the back of the eye,between the sclera and choroid;

FIG. 4E depicts a cross-sectional view of the eye of FIG. 4A, with theneedle of the instrument of FIG. 1 being advanced under directvisualization at the back of the eye, pressing against the outer surfaceof the choroid causing the choroid to “tent”;

FIG. 4F depicts a cross-sectional view of the eye of FIG. 4A, with theneedle dispensing a leading bleb under direct visualization at the backof the eye, the needle between the sclera and choroid, and the leadingbleb in the sub retinal space between the choroid and a retina;

FIG. 4G depicts a cross-sectional view of the eye of FIG. 4A, with theneedle dispensing a therapeutic agent to the eye at the back of the eye,between the sclera and choroid;

FIG. 5A depicts a detailed cross-sectional view of the eye of FIG. 4Adepicted in the state shown in FIG. 4E;

FIG. 5B depicts a detailed cross-sectional view of the eye of FIG. 4Adepicted in the state shown in FIG. 4F;

FIG. 5C depicts a detailed cross-sectional view of the eye of FIG. 4Adepicted in the state shown in FIG. 4G;

FIG. 6 depicts a cross-sectional view of the eye of FIG. 4A, with theinstrument of FIG. 1 at the back of the eye, between the sclera andchoroid, with the cannula of the instrument providing substantialseparation between the sclera and the choroid;

FIG. 7 depicts an enlarged view of the distal end of the cannula of theinstrument of FIG. 1 at the back of the eye, between the sclera andchoroid, with the cannula of the instrument providing substantialseparation between the sclera and the choroid, with the needle of theinstrument advanced to a distal position;

FIG. 8 depicts a side elevational view of the distal end of an exemplaryalternative needle that may be incorporated into the instrument of FIG.1;

FIG. 9A depicts a cross-sectional side view of the cannula of FIG. 2,with the cross-section taken along line 3-3 of FIG. 2, with the needleof FIG. 8 in a first longitudinal position;

FIG. 9B depicts a cross-sectional side view of the cannula of FIG. 2,with the cross-section taken along line 3-3 of FIG. 2, with the needleof FIG. 8 in a second longitudinal position;

FIG. 9C depicts a cross-sectional side view of the cannula of FIG. 2,with the cross-section taken along line 3-3 of FIG. 2, with the needleof FIG. 8 in a third longitudinal position;

FIG. 10 depicts an enlarged view of the distal end of the cannula of theinstrument of FIG. 1 at the back of the eye, between the sclera andchoroid, with the needle of FIG. 8 disposed in the cannula, with thecannula of the instrument providing substantial separation between thesclera and the choroid, and with the needle of FIG. 8 advanced to adistal position;

FIG. 11A depicts a cross-sectional side view of the needle of FIG. 8disposed in an exemplary alternative cannula that may be incorporatedinto the instrument of FIG. 1, with the needle in a proximal position;and

FIG. 11B depicts a cross-sectional side view of the needle of FIG. 8disposed in the cannula of FIG. 11A, with the needle in a distalposition.

The drawings are not intended to be limiting in any way, and it iscontemplated that various embodiments of the technology may be carriedout in a variety of other ways, including those not necessarily depictedin the drawings. The accompanying drawings incorporated in and forming apart of the specification illustrate several aspects of the presenttechnology, and together with the description serve to explain theprinciples of the technology; it being understood, however, that thistechnology is not limited to the precise arrangements shown.

DETAILED DESCRIPTION

The following description of certain examples of the technology shouldnot be used to limit its scope. Other examples, features, aspects,embodiments, and advantages of the technology will become apparent tothose skilled in the art from the following description, which is by wayof illustration, one of the best modes contemplated for carrying out thetechnology. As will be realized, the technology described herein iscapable of other different and obvious aspects, all without departingfrom the technology. Accordingly, the drawings and descriptions shouldbe regarded as illustrative in nature and not restrictive.

It is further understood that any one or more of the teachings,expressions, embodiments, examples, etc. described herein may becombined with any one or more of the other teachings, expressions,embodiments, examples, etc. that are described herein. Thefollowing-described teachings, expressions, embodiments, examples, etc.should therefore not be viewed in isolation relative to each other.Various suitable ways in which the teachings herein may be combined willbe readily apparent to those of ordinary skill in the art in view of theteachings herein. Such modifications and variations are intended to beincluded within the scope of the claims.

For clarity of disclosure, the terms “proximal” and “distal” are definedherein relative to a surgeon or other operator grasping a surgicalinstrument having a distal surgical end effector. The term “proximal”refers the position of an element closer to the surgeon or otheroperator and the term “distal” refers to the position of an elementcloser to the surgical end effector of the surgical instrument andfurther away from the surgeon or other operator.

I. EXEMPLARY INSTRUMENT FOR SUBRETINAL ADMINISTRATION OF THERAPEUTICAGENT

FIG. 1 shows an exemplary instrument (10) that is configured for use ina procedure for the subretinal administration of a therapeutic agent toan eye of a patient from a suprachoroidal approach. Instrument (10)comprises a body (20) and a flexible cannula (50) extending distallyfrom body (20). Cannula (50) of the present example has a generallyrectangular cross section, though any other suitable cross-sectionalprofile (e.g., elliptical, etc.) may be used. Cannula (50) is generallyconfigured to support a needle (100) that is slidable within cannula(50), as will be described in greater detail below.

In the present example, cannula (50) comprises a flexible material suchas Polyether block amide (PEBA), which may be manufactured under thetrade name PEBAX. Of course, any other suitable material or combinationof materials may be used. Also in the present example, cannula (50) hasa cross-sectional profile dimension of approximately 2.0 mm by 0.8 mm,with a length of approximately 80 mm. Alternatively, any other suitabledimensions may be used. As will be described in greater detail below,cannula (50) is flexible enough to conform to specific structures andcontours of the patient's eye, yet cannula (50) has sufficient columnstrength to permit advancement of cannula (50) between the sclera andchoroid of patient's eye without buckling. By way of example only,cannula (50) may be configured and operable in accordance with at leastsome of the teachings of U.S. Pub. No. 2015/0223977, entitled “Methodand Apparatus for Subretinal Administration of Therapeutic Agent,”published Aug. 13, 2015, the disclosure of which is incorporated byreference herein.

As can be seen in FIGS. 2-3B and 6, cannula (50) comprises a body (52),a closed distal end (54), and a lateral opening (56) that is locatedproximal to distal end (54). In the present example, distal end (54) hasa rounded configuration. It should be understood that distal end (54)may have any suitable kind of curvature. It should also be understoodthat distal end (54) may have any other suitable kind of configuration(e.g., beveled, etc.). In the present example, distal end (54) isconfigured to provide separation between the sclera and choroid layersto enable cannula (50) to be advanced between such layers while notinflicting trauma to the sclera or choroid layers. Also in the presentexample, the region of body (52) that defines lateral opening (56) isbeveled, as best seen in FIGS. 3A-3B. Alternatively, the edge of lateralopening (56) may have any other suitable configuration.

As best seen in FIGS. 3A-3B, a needle guide (60) is disposed within thehollow interior of cannula (50). By way of example only, needle guide(60) may be secured within cannula (50) by a press or interference fit,by adhesives, by mechanical locking mechanisms, and/or in any othersuitable fashion. Needle guide (60) includes a curved distal end (62)that leads to lateral opening (56) of cannula (50), such that a lumen(64) of needle guide (60) distally terminates at lateral opening (56).The portion of needle guide (60) that is proximal to distal end (62) issubstantially straight. Needle guide (60) may be formed of plastic,stainless steel, and/or any other suitable biocompatible material(s).

Needle (100) of the present example has a sharp distal tip (102) anddefines a lumen (104). Distal tip (102) of the present example has alancet configuration. In some other versions, distal tip (102) has atri-bevel configuration or any other configuration as described in U.S.Pub. No. 2015/0223977, entitled “Method and Apparatus for SubretinalAdministration of Therapeutic Agent,” published Aug. 13, 2015, thedisclosure of which is incorporated by reference herein. Still othersuitable forms that distal tip (102) may take will be apparent to thoseof ordinary skill in the art in view of the teachings herein. Needle(100) of the present example comprises a stainless steel hypodermicneedle that is sized to deliver the therapeutic agent while being smallenough to minimize incidental trauma as needle (100) penetrates tissuestructures of the patient's eye, as will be described in greater detailbelow. While stainless steel is used in the present example, it shouldbe understood that any other suitable material(s) may be used, includingbut not limited to nitinol, etc.

By way of example only, needle (100) may be 35 gauge with a 100 μm innerdiameter, although other suitable sizes may be used. For instance, theouter diameter of needle (100) may fall within the range of 27 gauge to45 gauge; or more particularly within the range of 30 gauge to 42 gauge;or more particularly within the range of 32 gauge to 39 gauge. Asanother merely illustrative example, the inner diameter of needle (100)may fall within the range of approximately 50 μm to approximately 200μm; or more particularly within the range of approximately 50 μm toapproximately 150 μm; or more particularly within the range ofapproximately 75 μm to approximately 125 μm.

Needle (100) is slidably disposed within lumen (64) of needle guide(60). Needle guide (60) is generally configured to direct needle (100)upwardly along an exit axis (EA) that is obliquely oriented relative tothe longitudinal axis (LA) of cannula (50) through lateral opening (56)of cannula (50). This is shown in the sequence depicted in FIGS. 3A-3B,in which FIG. 3A shows needle (100) in a proximal position (where distaltip (102) of needle (100) is fully contained in lumen (64) of needleguide (60)); and FIG. 3B shows needle (100) in a distal position (wheredistal tip (102) of needle (100) is outside of needle guide (60)). Whileneedle (100) is flexible, needle (100) of the present example isresiliently biased to assume a straight configuration. Thus, as shown inFIG. 3B, the portion of needle (100) that extends outside of cannula(50) and needle guide (60) is substantially straight, extending alongexit axis (EA). In particular, at least a substantial length of theportion of needle (100) that extends outside of cannula (50) and needleguide (60) is coaxially aligned with exit axis (EA).

It should be understood that the depiction of exit axis (EA) in FIGS.3A-3B may be somewhat exaggerated, for illustrative purposes only. Insome versions, curved distal end (62) is configured to direct needle(100) along an exit axis (EA) that extends distally from cannula (50) atan angle of approximately 7° to approximately 9° relative to thelongitudinal axis (LA) of cannula (50). It should be understood thatsuch an angle may be desirable to deflect needle (100) in a direction toensure penetration of needle into the choroid and to minimize thepossibility of needle (100) continuing beneath the choroid through thesuprachoroidal space (as opposed to penetrating through the choroid) andthe possibility of retinal perforation. By way of further example only,curved distal portion (88) may urge needle (100) to exit cannula (50)along an exit axis (EA) that is oriented at an angle within the range ofapproximately 5° to approximately 30° relative to the longitudinal axis(LA) of cannula (50); or more particularly within the range ofapproximately 5° to approximately 20° relative to the longitudinal axis(LA) of cannula (50); or more particularly within the range ofapproximately 5° to approximately 10° relative to the longitudinal axis(LA) of cannula (50).

As shown in FIG. 1, instrument (10) of the present example furthercomprises an actuation knob (26) located at the proximal end of body(20). Actuation knob (26) is rotatable relative to body (20) to therebyselectively translate needle (100) longitudinally relative to cannula(50). In particular, actuation knob (26) is rotatable in a first angulardirection to drive needle (100) distally relative to cannula (50); andin a second angular direction to drive needle (100) proximally relativeto cannula (50). By way of example only, instrument (10) may providesuch functionality through knob (26) in accordance with at least some ofthe teachings of U.S. Pub. No. 2015/0223977, entitled “Method andApparatus for Subretinal Administration of Therapeutic Agent,” publishedAug. 13, 2015, the disclosure of which is incorporated by referenceherein. Alternatively, any other suitable kind of actuation feature(s)may be used to drive needle (100) longitudinally relative to cannula(50).

In the present example, knob (26) is rotatable through a complete rangeof motion that corresponds to advancement of needle (100) to a positionrelative to cannula (50) to a predetermined amount of penetration withinan eye of a patient. In other words, instrument (10) is configured suchthat an operator rotates knob (26) until knob (26) can no longer rotate,or until knob (26) begins to slip or “freewheel” in a clutch assembly,to properly position needle (100) within an eye of a patient. In someexamples, the predetermined amount of advancement of needle (100)relative to cannula (50) is between approximately 0.25 mm toapproximately 10 mm; or more particularly within the range ofapproximately 0.1 mm to approximately 10 mm; or more particularly withinthe range of approximately 2 mm to approximately 6 mm; or moreparticularly to approximately 4 mm.

In addition or in the alternative, instrument (10) may be equipped withcertain tactile feedback features to indicate to an operator when needle(100) has been advanced to certain predetermined distances relative tocannula (50). Accordingly, an operator may determine the desired depthof penetration of needle (100) into a patient's eye based on directvisualization of indicia on instrument and/or based on tactile feedbackfrom instrument (10). Of course, such tactile feedback features may becombined with the present example, as will be apparent to those ofordinary skill in the art in view of the teachings herein.

As also shown in FIG. 1, a pair of supply tubes (30, 40) extendproximally from actuator knob (26). In the present example, first supplytube (30) is configured to couple with a source of bleb fluid (340)(e.g., BSS); while second supply tube (40) is configured to couple witha source of therapeutic agent (341). It should be understood that eachfluid supply tube (30, 40) may include a conventional luer featureand/or other structures permitting fluid supply tubes (30, 40) to becoupled with respective fluid sources. Fluid supply tubes (30, 40) leadto a valve assembly that includes actuation arms (24). Actuation arms(24) are pivotable to selectively change the state of the valveassembly. Based on the pivotal position of actuation arms (24), thevalve assembly is operable to selectively pinch or otherwise open/closethe supply of fluid from fluid supply tubes (30, 40) to lumen (104) ofneedle (100). Thus, actuation arms (24) are operable to selectivelycontrol the delivery of bleb fluid (340) and therapeutic agent (341) vianeedle (100). By way of example only, the valve assembly may beconfigured and operable in accordance with at least some of theteachings of U.S. Pub. No. 2015/0223977, entitled “Method and Apparatusfor Subretinal Administration of Therapeutic Agent,” published Aug. 13,2015, the disclosure of which is incorporated by reference herein. Othersuitable features and configurations that may be used to control fluiddelivery via needle (100) will be apparent to those of ordinary skill inthe art in view of the teachings herein.

It should be understood that the features and operability of instrument(10) may be varied in numerous ways. By way of example only, needle(100) may be replaced with needle (200) as described in greater detailbelow. In addition, cannula (50) may be replaced with cannula (400) aswill be described in greater detail below. In addition, instrument (10)may be modified in accordance with at least some of the teachings ofU.S. Pub. No. 2015/0223977, entitled “Method and Apparatus forSubretinal Administration of Therapeutic Agent,” published Aug. 13,2015, the disclosure of which is incorporated by reference herein; U.S.Pub. No. 2015/0351958, entitled “Therapeutic Agent Delivery Device withConvergent Lumen,” published Dec. 10, 2015, the disclosure of which isincorporated by reference herein; U.S. Pub. No. 2015/0351959, entitled“Sub-Retinal Tangential Needle Catheter Guide and Introducer,” publishedDec. 10, 2015, the disclosure of which is incorporated by referenceherein; U.S. Pub. No. 2016/0074212, entitled “Method and Apparatus forSensing Position Between Layers of an Eye,” published Mar. 17, 2016, thedisclosure of which is incorporated by reference herein; U.S. Pub. No.2016/0074217, entitled “Motorized Suprachoroidal Injection ofTherapeutic Agent,” published Mar. 17, 2016, the disclosure of which isincorporated by reference herein; U.S. Pub. No. 2016/0074211, entitled“Therapeutic Agent Delivery Device with Advanceable Cannula and Needle,”published Mar. 17, 2016, the disclosure of which is incorporated byreference herein; and/or U.S. Pub. No. 2016/0081849, entitled“Therapeutic Agent Delivery Device,” published Mar. 24, 2016, thedisclosure of which is incorporated by reference herein. Other suitablemodifications will be apparent to those of ordinary skill in the art inview of the teachings herein.

II. EXEMPLARY PROCEDURE FOR SUBRETINAL ADMINISTRATION OF THERAPEUTICAGENT

FIGS. 4A-5C show an exemplary procedure for subretinal delivery oftherapeutic agent from a suprachoroidal approach using instrument (10)described above. By way of example only, the method described herein maybe employed to treat macular degeneration and/or other ocularconditions. Although the procedure described herein is discussed in thecontext of the treatment of age-related macular degeneration, it shouldbe understood that no such limitation is intended or implied. Forinstance, in some merely exemplary alternative procedures, the sametechniques described herein may be used to treat retinitis pigmentosa,diabetic retinopathy, and/or other ocular conditions. Additionally, itshould be understood that the procedure described herein may be used totreat either dry or wet age-related macular degeneration.

In the present example, the procedure begins by an operator immobilizingtissue surrounding a patient's eye (301) (e.g., the eyelids) using aspeculum, and/or any other instrument suitable for immobilization. Whileimmobilization described herein with reference to tissue surrounding eye(301), it should be understood that eye (301) itself may remain free tomove. Once the tissue surrounding eye (301) has been immobilized, an eyechandelier port (314) is inserted into eye (301), as shown in FIG. 4A,to provide intraocular illumination when the interior of eye (301) isviewed through the pupil. In the present example, eye chandelier port(314) is positioned in the inferior medial quadrant such that a superiortemporal quadrant sclerotomy may be preformed. Eye chandelier port (314)is positioned to direct light onto the interior of eye (301) toilluminate at least a portion of the retina (e.g., including at least aportion of the macula). As will be understood, such illuminationcorresponds to an area of eye (301) that is being targeted for deliveryof therapeutic agent.

In the present example, only chandelier port (314) is inserted at thestage shown in FIG. 4A, without yet inserting an optical fiber (315)into port (314). In some other versions, an optical fiber (315) may beinserted into chandelier port (314) at this stage. In either case, amicroscope may optionally be utilized to visually inspect the eye toconfirm proper positioning of eye chandelier port (314) relative to thetarget site. Although FIG. 4A shows a particular positioning of eyechandelier port (314), it should be understood that eye chandelier port(314) may have any other positioning as will be apparent to those ofordinary skill in the art in view of the teachings herein.

Once eye chandelier port (314) has been positioned, the sclera (304) maybe accessed by dissecting the conjunctiva by incising a flap in theconjunctiva and pulling the flap posteriorly. After such a dissection iscompleted, the exposed surface (305) of the sclera (304) may optionallybe blanched using a cautery tool to minimize bleeding. Once conjunctivadissection is complete, the exposed surface (305) of the sclera (304)may optionally be dried using a WECK-CEL or other suitable absorbentdevice. A template may then be used to mark eye (301), as described inU.S. Pub. No. 2015/0223977, entitled “Method and Apparatus forSubretinal Administration of Therapeutic Agent,” published Aug. 13,2015, the disclosure of which is incorporated by reference herein. Anoperator may then use a visual guide created using the template toattach a suture loop assembly (332) and to perform a sclerotomy, asshown in FIG. 4B, using a conventional scalpel (313) or other suitablecutting instrument. The sclerotomy procedure forms a small incisionthrough sclera (304) of eye (301). The sclerotomy is preformed withparticular care to avoid penetration of the choroid (306). Thus, thesclerotomy procedure provides access to the space between sclera (304)and choroid (306). Once the incision is made in eye (301), a bluntdissection may optionally be performed to locally separate sclera (304)from choroid (306). Such a dissection may be performed using a smallblunt elongate instrument, as will be apparent to those of ordinaryskill in the art in view of the teachings herein.

With the sclerotomy procedure performed, an operator may insert cannula(50) of instrument (10) through incision (316) and into the spacebetween sclera (304) and choroid (306). As can be seen in FIG. 4C,cannula (50) is directed through suture loop assembly (332) and into theincision. Suture loop assembly (332) may stabilize cannula (50) duringinsertion. Additionally, suture loop assembly (332) maintains cannula(50) in a generally tangential orientation relative to the incision.Such tangential orientation may reduce trauma as cannula (50) is guidedthrough the incision. As cannula (50) is inserted into the incisionthrough suture loop assembly (332), an operator may use forceps or otherinstruments to further guide cannula (50) along an atraumatic path. Ofcourse, use of forceps or other instruments is merely optional, and maybe omitted in some examples.

Although not shown, it should be understood that in some examplescannula (50) may include one or more markers on the surface of cannula(50) to indicate various depths of insertion. While merely optional,such markers may be desirable to aid an operator in identifying theproper depth of insertion as cannula (50) is guided along an atraumaticpath. For instance, the operator may visually observe the position ofsuch markers in relation to suture loop assembly (332) and/or inrelation to the incision in the sclera (304) as an indication of thedepth to which cannula (50) is inserted in eye (301). By way of exampleonly, one such marker may correspond to an approximately 6 mm depth ofinsertion of cannula (50).

As shown in FIG. 4D, once cannula (50) is at least partially insertedinto eye (301), an operator may insert an optical fiber (315) into eyechandelier port (314) if the fiber (315) had not yet been inserted atthis stage. With eye chandelier port (314) in place and assembled withoptical fiber (315), an operator may activate eye chandelier port (314)by directing light through optical fiber (315) to provide illuminationof eye (301) and thereby visualize the interior of eye (301). Furtheradjustments to the positioning of cannula (50) may optionally be made atthis point to ensure proper positioning relative to the area ofgeographic atrophy of retina (308). In some instances, the operator maywish to rotate the eye (301), such as by pulling on suture loop assembly(332), to direct the pupil of the eye (301) toward the operator in orderto optimize visualization of the interior of the eye (301) via thepupil.

FIGS. 4C-4D show cannula (50) as it is guided between sclera (304) andchoroid (306) to the delivery site for the therapeutic agent. In thepresent example, the delivery site corresponds to a generally posteriorregion of eye (301) adjacent to an area of geographic atrophy of retina(308). In particular, the delivery site of the present example issuperior to the macula, in the potential space between the neurosensoryretina and the retinal pigment epithelium layer. By way of example only,the operator may rely on direct visualization through a microscopedirected through the pupil of eye (301) as cannula (50) is beingadvanced through the range of motion shown in FIGS. 4C-4D, withillumination provided through fiber (315) and port (314). Cannula (50)may be at least partially visible through a retina (308) and choroid(306) of eye (301). Visual tracking may be enhanced in versions where anoptical fiber is used to emit visible light through the distal end ofcannula (50).

Once cannula (50) has been advanced to the delivery site as shown inFIG. 4D, an operator may advance needle (100) of instrument (10) asdescribed above by actuating knob (26). As can be seen in FIGS. 4E and5A, needle (100) is advanced relative to cannula (50) such that needle(100) pierces through choroid (306) without penetrating retina (308).Immediately prior to penetrating choroid (306), needle (100) may appearunder direct visualization as “tenting” the surface of choroid (306). Inother words, needle (100) may deform choroid (306) by pushing upwardlyon choroid (306), providing an appearance similar to a tent poledeforming the roof of a tent. Such a visual phenomenon may be used by anoperator to identify whether choroid (306) is about to be pierced andthe location of any eventual piercing. The particular amount of needle(100) advancement sufficient to initiate “tenting” and subsequentpiercing of choroid (306) may be of any suitable amount as may bedetermined by a number of factors such as, but not limited to, generalpatient anatomy, local patient anatomy, operator preference, and/orother factors. As described above, a merely exemplary range of needle(100) advancement may be between approximately 0.25 mm and approximately10 mm; or more particularly between approximately 2 mm and approximately6 mm.

In the present example, after the operator has confirmed that needle(100) has been properly advanced by visualizing the tenting effectdescribed above, the operator infuses a balanced salt solution (BSS) orother similar solution as needle (100) is advanced relative to cannula(50). Such a BSS may form a leading bleb (340) ahead of needle (100) asneedle (100) is advanced through choroid (306). Leading bleb (340) maybe desirable for two reasons. First, as shown in FIGS. 4F and 5B,leading bleb (340) may provide a further visual indicator to an operatorto indicate when needle (100) is properly positioned at the deliverysite. Second, leading bleb (340) may provide a barrier between needle(100) and retina (308) once needle (100) has penetrated choroid (306).Such a barrier may push the retinal wall outwardly, thereby minimizingthe risk of retinal perforation as needle (100) is advanced to thedelivery site. In some versions, a foot pedal is actuated in order todrive leading bleb (340) out from needle (100). Alternatively, othersuitable features that may be used to drive leading bleb (340) out fromneedle (100) will be apparent to those of ordinary skill in the art inview of the teachings herein.

Once the operator visualizes leading bleb (340), the operator may ceaseinfusion of BSS, leaving a pocket of fluid as can be seen in FIGS. 4Fand 5B. Next, a therapeutic agent (341) may be infused by actuating asyringe or other fluid delivery device as described in variousreferences cited herein. The particular therapeutic agent (341)delivered may be any suitable therapeutic agent configured to treat anocular condition. Some merely exemplary suitable therapeutic agents mayinclude, but are not necessarily limited to, drugs having smaller orlarge molecules, therapeutic cell solutions, certain gene therapysolutions, tissue plasminogen activators, and/or any other suitabletherapeutic agent as will be apparent to those of ordinary skill in theart in view of the teachings herein. By way of example only, thetherapeutic agent (341) may be provided in accordance with at least someof the teachings of U.S. Pat. No. 7,413,734, entitled “Treatment ofRetinitis Pigmentosa with Human Umbilical Cord Cells,” issued Aug. 19,2008, the disclosure of which is incorporated by reference herein. Inaddition to, or as an alternative to, being used to deliver atherapeutic agent (341), instrument (10) and variations thereof may beused to provide drainage and/or perform other operations.

In the present example, the amount of therapeutic agent (341) that isultimately delivered to the delivery site is approximately 50 μL,although any other suitable amount may be delivered. In some versions, afoot pedal is actuated in order to drive agent (341) out from needle(100). Alternatively, other suitable features that may be used to driveagent (341) out from needle (100) will be apparent to those of ordinaryskill in the art in view of the teachings herein. Delivery oftherapeutic agent (341) may be visualized by an expansion of the pocketof fluid as can be seen in FIGS. 4G and 5C. As shown, therapeutic agent(341) essentially mixes with the fluid of leading bleb (340) astherapeutic agent (341) is injected into the surprachoroidal, subretinalspace.

Once delivery is complete, needle (100) may be retracted by rotatingknob (26) in a direction opposite to that used to advance needle (100);and cannula (50) may then be withdrawn from eye (301). It should beunderstood that because of the size of needle (100), the site whereneedle (100) penetrated through choroid (306) is self sealing, such thatno further steps need be taken to seal the delivery site through choroid(306). Suture loop assembly (332) and chandelier (314) may be removed,and the incision in the sclera (304) may be closed using any suitableconventional techniques.

As noted above, the foregoing procedure may be carried out to treat apatient having macular degeneration. In some such instances, thetherapeutic agent (341) that is delivered by needle (100) may comprisecells that are derived from postpartum umbilicus and placenta. As notedabove, and by way of example only, the therapeutic agent (341) may beprovided in accordance with at least some of the teachings of U.S. Pat.No. 7,413,734, entitled “Treatment of Retinitis Pigmentosa with HumanUmbilical Cord Cells,” issued Aug. 19, 2008, the disclosure of which isincorporated by reference herein. Alternatively, needle (100) may beused to deliver any other suitable substance or substances, in additionto or in lieu of those described in U.S. Pat. No. 7,413,734 and/orelsewhere herein. By way of example only, therapeutic agent (341) maycomprise various kinds of drugs including but not limited to smallmolecules, large molecules, cells, and/or gene therapies. It should alsobe understood that macular degeneration is just one merely illustrativeexample of a condition that may be treated through the proceduredescribed herein. Other biological conditions that may be addressedusing the instruments and procedures described herein will be apparentto those of ordinary skill in the art.

It should also be understood that the procedure described above may becarried out in accordance with any of the teachings of U.S. Pub. No.2015/0223977, entitled “Method and Apparatus for SubretinalAdministration of Therapeutic Agent,” published Aug. 13, 2015, thedisclosure of which is incorporated by reference herein; U.S. Pub. No.2015/0351958, entitled “Therapeutic Agent Delivery Device withConvergent Lumen,” published Dec. 10, 2015, the disclosure of which isincorporated by reference herein; U.S. Pub. No. 2015/0351959, entitled“Sub-Retinal Tangential Needle Catheter Guide and Introducer,” publishedDec. 10, 2015, the disclosure of which is incorporated by referenceherein; U.S. Pub. No. 2016/0074212, entitled “Method and Apparatus forSensing Position Between Layers of an Eye,” published Mar. 17, 2016, thedisclosure of which is incorporated by reference herein; U.S. Pub. No.2016/0074217, entitled “Motorized Suprachoroidal Injection ofTherapeutic Agent,” published Mar. 17, 2016, the disclosure of which isincorporated by reference herein; U.S. Pub. No. 2016/0074211, entitled“Therapeutic Agent Delivery Device with Advanceable Cannula and Needle,”published Mar. 17, 2016, the disclosure of which is incorporated byreference herein; and/or U.S. Pub. No. 2016/0081849, entitled“Therapeutic Agent Delivery Device,” published Mar. 24, 2016, thedisclosure of which is incorporated by reference herein.

III. EXEMPLARY ALTERNATIVE NEEDLE FOR INSTRUMENT

Several variables may affect the relationship between the exit angle(EA) of needle (100) and the choroid (306) of any given patient. Itshould be understood that the choroid (306) and the retina (308) arevery thin and have relatively little structural integrity. Thus, evenwhen a very flexible cannula (50) is used, cannula (50) may tend toprovide substantial separation between the choroid (306) and the sclera(304) as cannula (50) is inserted between the choroid (306) and thesclera (304). The degree of separation may vary from patient to patient(e.g., based on normal anatomical variation and/or based on thepatient's disease state, etc.). In cases where the separation is trulysubstantial, the exit angle (EA) of needle (100) may be insufficient toresult in distal tip (102) passing fully through the choroid (306). Inother words, needle (100) may continue through the suprachoroidal spacewithout fully penetrating the choroid (306).

FIG. 6 shows an exemplary scenario where cannula (50) has elevated thechoroid (306) and retina (308) away from the sclera (304) to the pointwhere a substantial gap (305) is defined between the sclera (304) andthe choroid (306). As also shown in FIG. 6, the exit angle (EA) isoriented such that needle (100) would not penetrate the choroid (306);and further such that needle (100) would eventually engage the sclera(304). FIG. 7 shows needle (100) advanced distally along this exit angle(EA). As shown, needle (100) passes tangentially along the choroid (306)without ever breaching the choroid (306). In some other instances,needle (100) may pass partially through the choroid (306) andimmediately exit the choroid (306) without ever reaching the subretinalspace between the choroid (306) and the retina (308).

If the operator determines (e.g., based on the absence of a choroidal“tenting” observation as described above) that needle (100) has notfully penetrated the choroid (306) despite needle (100) being advancedfully distally, the operator may retract needle (100) proximally,slightly reposition cannula (50) and/or another portion of instrument(10) in order to provide a better orientation for the exit angle (EA),and then try advancing needle (100) distally again. Even with suchefforts, it may still be very difficult or even impossible in some casesto successfully penetrate the choroid (306) with needle (100). Even incases where efforts to reposition are successful, the success rate maybe highly dependent on the skill of the operator, and the repositioningefforts will add time to the procedure. Moreover, the repositioning mayincrease the risk of tissue trauma, increase the risk of bleb collapse,and/or increase the risk of cell egress into the suprachoroidal space.

It may seem apparent to address the above-noted issues by simplymodifying needle guide (60) to provide a steeper exit angle (EA).However, this kind of modification may be unsuitable for many patients.In particular, increasing the exit angle (EA) by providing a morepronounced bend in distal end (62) of needle guide (60) may increase therisk of needle (100) perforating the retina (308) in some patients,particularly in those where the gap (305) created by cannula (50)between the sclera (304) and the choroid (306) is less pronounced thanthe gap (305) shown in FIGS. 6-7; including cases where the gap (305) isnon-existent. It may therefore be desirable to provide a more nuancedsolution that provides greater consistency in penetration of the choroid(306) without substantially increasing the risk of penetration of theretina (308). Such a solution may provide better accommodation ofanatomical variations across patients; accommodate variation in operatortechnique and expertise; and minimize the level of operator trainingrequired.

FIG. 8 shows an exemplary alternative needle (200) that may beincorporated into instrument (10) in place of needle (100). In someinstances, needle (200) may be substituted for needle (100) withoutmodifying any other aspects of instrument (10). Needle (200) of thepresent example has a distal tip (202) that is configured and operablejust like distal tip (102) described above. As shown in FIGS. 9A-9C,needle (200) also defines a lumen (204) that is configured and operablejust like lumen (104) described above. Unlike needle (100), however,needle (200) of the present example includes a substantially straightproximal portion (210), a substantially straight distal portion (212),and a bent portion (214) located between proximal and distal portions(210, 212). In the present example, needle (200) is formed of nitinol,though it should be understood that any other suitable material(s)(e.g., stainless steel, etc.) may be used.

Needle (200) is configured to provide bent portion (214) as a preformedfeature, such that needle (200) is resiliently biased to assume theconfiguration shown in FIG. 6. By way of example only, bent portion(214) may be configured to have a constant radius of curvature betweenapproximately 4 mm and approximately 15 mm; a constant radius ofcurvature between approximately 7 mm and approximately 12 mm; a constantradius of curvature between approximately 8 mm and approximately 11 mm;or a constant radius of curvature between approximately 9 mm andapproximately 10 mm. In some versions, bent portion (214) has a radiusof curvature of approximately 10.5 mm. In some other versions, bentportion (214) has a radius of curvature of approximately 10.0 mm. Insome other versions, bent portion (214) has a radius of curvature ofapproximately 9.5 mm. It should be understood that the radius ofcurvature must be carefully selected because if the radius is too small,there may be an increased risk of perforating the retina (308); and ifthe radius is too large, the needle (200) may still fail to fullypenetrate the choroid (306).

While the radius of curvature of bent portion (214) is constant in thepresent example, in some other versions the radius of curvature may bevariable. For instance, some variations of needle (200) may provide alarger radius of curvature in a region of needle (200) that remainsdisposed in cannula (50), even when needle (200) is in a distallyextended position; with a smaller radius of curvature in a region ofneedle (200) that extends distally from cannula (50) when needle (200)is in a distally extended position. This kind of configuration mayimpart a slight precurvature to cannula (50), which may further assistin cannula (50) conforming to the curved inner wall of sclera (304),which may in turn reduce the occurrence (or magnitude) of gap (305).

As shown in FIGS. 9A-9C, needle (200) is slidably disposed in needleguide (60) within cannula (50). While FIG. 9A shows needle (200) in apartially advanced state, it should be understood that needle (200) maybe retracted further proximally in needle guide (60) such that distaltip (202) does not protrude through lateral opening (56). As shown inFIG. 9A, as needle (200) begins to exit cannula (50) via lateral opening(56), the distally protruding portion of needle (200) is oriented alonga first exit axis (EA₁). At this stage, bent portion (214) and part ofdistal portion (212) are still contained within needle guide (60), suchthat needle guide (60) prevents needle (200) from reaching theconfiguration shown in FIG. 8.

As the operator continues to advance needle (200) distally relative tocannula (50), more of needle (200) protrudes distally from lateralopening (56), as shown in FIG. 9B. Due to the resilient bias of needle(200), the now longer protruding portion of needle (200) is orientedalong a second exit axis (EA₂). Second exit axis (EA₂) defines an anglewith the longitudinal axis (LA) that is larger than the angle definedbetween first exit axis (EA₁) and the longitudinal axis (LA). As theoperator continues to advance needle (200) further distally relative tocannula (50), even more of needle (200) protrudes distally from lateralopening (56), as shown in FIG. 9C. Due to the resilient bias of needle(200), the now longer protruding portion of needle (200) is orientedalong a third exit axis (EA₃). Third exit axis (EA₃) defines an anglewith the longitudinal axis (LA) that is larger than the angle definedbetween second exit axis (EA₃) and the longitudinal axis (LA). Thus, thefurther needle (200) is advanced, the larger the angle defined betweenthe exit axis (EA) and the longitudinal axis (LA). It should beunderstood that the depictions of exit axes (EA₁, EA₂, EA₃) in FIGS.9A-9C may be somewhat exaggerated, for illustrative purposes only.

As shown in FIG. 10, needle (200) may be particularly useful in caseswhere cannula creates a substantial gap (305) between the sclera (304)and the choroid (306). It should be understood that the gap (305) inFIG. 10 is substantially the same as the gap (305) in FIG. 7. As notedabove, due to the gap (305) in FIG. 7 and the associated relationshipsbetween the anatomical structures and the instrument (10) structures,needle (100) is unable to penetrate choroid (306). However, as shown inFIG. 10, the curvature of needle (200) allows needle (200) to penetratechoroid (306) despite the presence of gap (305) and the associatedrelationships between the anatomical structures and the instrument (10)structures.

As noted above, the exit angle (EA) of needle (200) varies based on theextent to which needle (200) is extended from cannula (50). It should beunderstood that this variation in the exit angle (EA) will allow theoperator to control the optimal exit angle (EA) by controlling theamount of needle (200) extension. This may allow for shallower angles(less extension) for some patients and steeper angles (more extension)for other patients, to more consistently be able to achieve penetrationof the choroid (306) in a relatively safe and efficient manner,eliminating the need for other mitigations or workarounds that wouldotherwise be required from the scenario depicted in FIG. 7.

IV. EXEMPLARY CANNULA NEEDLE FOR INSTRUMENT

As noted above, cannula (50) includes a closed distal end (54) and alateral opening (56) that is located proximal to distal end (54). Insome instances, it may be desirable to provide an alternative cannulathat has an open distal end, without a lateral opening. By way ofexample only, this may provide simplified manufacturing processes. Sinceit may still be desirable to have a needle exit the cannula at such thatthe distal tip of the needle is oriented along an axis that is obliqueto the longitudinal axis of the cannula, it may be desirable to use aneedle with a preformed curve in versions where the cannula has an opendistal end.

FIG. 11A shows an exemplary alternative cannula (400) that may bereadily incorporated into instrument (10) in place of cannula (50).Cannula (400) of this example has a flexible body (402) and a distalopening (406). Distal opening (406) is coaxially positioned on thelongitudinal axis of cannula (400) in this example. In some otherversions, distal opening (406) is offset from the longitudinal axis ofcannula (400). By way of example only, cannula (400) may be formed ofPolyether block amide (PEBA) and/or any other suitable kind(s) ofmaterial(s). Like cannula (50), cannula (400) of the present example hassufficient column strength to be advanced distally between the sclera(306) and choroid (308) of patient's eye without buckling.

An insert (408) is positioned within cannula (400). Insert (408) may besecured within cannula (400) by a press or interference fit, byadhesives, by mechanical locking mechanisms, and/or in any othersuitable fashion. In the present example, insert (408) is formed of apolyimide material, though it should be understood that any othersuitable biocompatible material(s) may be used. Insert (408) of thepresent example is substantially straight yet may bend with cannula(400). Needle (200) is slidably disposed in a lumen (410) defined byinsert (408). When needle (200) is in a proximal position as shown inFIG. 11A, distal tip (202) of needle (200) is fully contained withinlumen (410). At this stage, insert (408) constrains needle (200) suchthat needle (200) is held under stress in a substantially straightconfiguration. When needle (200) is in a distal position as shown inFIG. 11B, distal tip (202) of needle is positioned distally of cannula(400). At this stage, curved portion (214) is exposed such that thedistal portion (212) of needle (200) is oriented along an exit axis thatis oblique to the longitudinal axis of cannula (400). It should beunderstood that this configuration and orientation may position distaltip (202) at the subretinal space (i.e., between the choroid (306) andthe retina (308)).

V. EXEMPLARY COMBINATIONS

The following examples relate to various non-exhaustive ways in whichthe teachings herein may be combined or applied. It should be understoodthat the following examples are not intended to restrict the coverage ofany claims that may be presented at any time in this application or insubsequent filings of this application. No disclaimer is intended. Thefollowing examples are being provided for nothing more than merelyillustrative purposes. It is contemplated that the various teachingsherein may be arranged and applied in numerous other ways. It is alsocontemplated that some variations may omit certain features referred toin the below examples. Therefore, none of the aspects or featuresreferred to below should be deemed critical unless otherwise explicitlyindicated as such at a later date by the inventors or by a successor ininterest to the inventors. If any claims are presented in thisapplication or in subsequent filings related to this application thatinclude additional features beyond those referred to below, thoseadditional features shall not be presumed to have been added for anyreason relating to patentability.

Example 1

An apparatus, comprising: (a) a body; (b) a cannula extending distallyfrom the body, wherein the cannula is flexible; and (c) a needleslidably disposed in the cannula, wherein the needle includes: (i) asharp distal tip, wherein the needle is configured to translate relativeto the cannula between a proximal position and a distal position,wherein the distal tip is configured to be positioned inside the cannulawhen the needle is in the proximal position, wherein the distal tip isconfigured to be positioned outside the cannula when the needle is inthe distal position, and (ii) a curved portion, wherein the needle isresiliently biased to extend along a curve through the curved portion.

Example 2

The apparatus of Example 1, wherein the cannula includes: (i) a closeddistal end, and (ii) a lateral opening located proximal to the closeddistal end.

Example 3

The apparatus of Example 2, wherein the cannula further includes a rampfeature, wherein the ramp feature extends from an interior region of thecannula to the lateral opening.

Example 4

The apparatus of any one or more of Examples 1 through 3, wherein thecurved portion is resiliently biased to define a constant radius ofcurvature.

Example 5

The apparatus of Example 4, wherein the radius of curvature is betweenapproximately 7 mm and approximately 12 mm.

Example 6

The apparatus of Example 4, wherein the radius of curvature is betweenapproximately 4 mm and approximately 15 mm.

Example 7

The apparatus of Example 4, wherein the radius of curvature is betweenapproximately 9 mm and approximately 10 mm.

Example 8

The apparatus of any one or more of Examples 1 through 7, wherein thecurved portion is configured to position the distal tip at aprogressively increasing exit angle relative to a longitudinal axis ofthe cannula, based on a distance to which the needle is advanceddistally relative to the cannula.

Example 9

The apparatus of any one or more of Examples 1 through 8, wherein thecurved portion comprises a first curved region and a second curvedregion, wherein the first curved region is located near a distal portionof the needle, wherein the second curved region is located proximal tothe first curved region.

Example 10

The apparatus of Example 9, wherein the first curved region has a firstradius of curvature, wherein the second curved region has a secondradius of curvature, wherein the second radius of curvature is greaterthan the first radius of curvature.

Example 11

The apparatus of any one or more of Examples 9 through 10, wherein thefirst curved region is configured to not impart a curvature to thecannula, wherein the second curved region is configured to impart acurvature to the cannula.

Example 12

The apparatus of any one or more of Examples 1 through 11, wherein theneedle further includes a straight proximal portion and a straightdistal portion, wherein the curved portion is longitudinally positionedbetween the straight proximal portion and the straight distal portion.

Example 13

The apparatus of any one or more of Examples 1 through 12, wherein thecannula defines an open distal end.

Example 14

The apparatus of Example 13, wherein the needle is configured toprotrude from the open distal end of the cannula when the needle is inthe distal position.

Example 15

The apparatus of any one or more of Examples 1 through 14, furthercomprising a source of liquid therapeutic agent, wherein the needle isoperable to deliver the liquid therapeutic agent.

Example 16

The apparatus of Example 15, wherein the body includes: (i) a needleactuator, wherein the actuator is operable to drive the needlelongitudinally relative to the cannula, and (ii) a valve member, whereinthe valve member is operable to selectively provide fluid communicationfrom the source of liquid therapeutic agent to the needle.

Example 17

An apparatus, comprising: (a) a body; (b) a cannula extending distallyfrom the body, wherein the cannula is flexible, wherein the cannulaincludes: (i) a closed distal end, and (ii) a lateral opening locatedproximal to the closed distal end; and (c) a needle slidably disposed inthe cannula, wherein the needle includes: (i) a sharp distal tip,wherein the needle is configured to translate relative to the cannulabetween a proximal position and a distal position, wherein the distaltip is configured to be positioned inside the cannula when the needle isin the proximal position, wherein the distal tip is configured extendpast the lateral opening when the needle is in the distal position, and(ii) a curved portion, wherein the curved portion is configured toprovide an oblique exit angle to a portion of the needle extending pastthe lateral opening when the needle is in the distal position.

Example 18

The apparatus of Example 17, wherein the curved portion is resilientlybiased to assume a curved configuration, wherein the curved portion isfurther configured to deform to a substantially straight configurationwithin the cannula when the needle is in the proximal position.

Example 19

A method of administering a therapeutic agent to an eye of a patient,wherein the eye includes a sclera, a choroid, and a retina, the methodcomprising: (a) inserting a flexible cannula between the sclera and thechoroid; (b) advancing a needle relative to the cannula, therebypenetrating the choroid with a distal tip of the needle, wherein theneedle includes a preformed curve, wherein the curve guides the needletoward a targeted region of the choroid; and (c) administering thetherapeutic agent to a region between the choroid and the retina via theneedle.

Example 20

The method of Example 19, wherein the act of advancing the needleincludes: (i) advancing the needle to a first longitudinal positionrelative to the cannula, wherein the needle defines a first exit anglerelative to the cannula at the first longitudinal position, and (ii)advancing the needle further distally to a second longitudinal positionrelative to the cannula, wherein the needle defines a second exit anglerelative to the cannula at the second longitudinal position, wherein thesecond exit angle is greater than the first exit angle.

VI. MISCELLANEOUS

It should be understood that any of the versions of the instrumentsdescribed herein may include various other features in addition to or inlieu of those described above. By way of example only, any of thedevices herein may also include one or more of the various featuresdisclosed in any of the various references that are incorporated byreference herein.

It should be understood that any one or more of the teachings,expressions, embodiments, examples, etc. described herein may becombined with any one or more of the other teachings, expressions,embodiments, examples, etc. that are described herein. Theabove-described teachings, expressions, embodiments, examples, etc.should therefore not be viewed in isolation relative to each other.Various suitable ways in which the teachings herein may be combined willbe readily apparent to those of ordinary skill in the art in view of theteachings herein. Such modifications and variations are intended to beincluded within the scope of the claims.

It should be appreciated that any patent, publication, or otherdisclosure material, in whole or in part, that is said to beincorporated by reference herein is incorporated herein only to theextent that the incorporated material does not conflict with existingdefinitions, statements, or other disclosure material set forth in thisdisclosure. As such, and to the extent necessary, the disclosure asexplicitly set forth herein supersedes any conflicting materialincorporated herein by reference. Any material, or portion thereof, thatis said to be incorporated by reference herein, but which conflicts withexisting definitions, statements, or other disclosure material set forthherein will only be incorporated to the extent that no conflict arisesbetween that incorporated material and the existing disclosure material.

Versions described above may be designed to be disposed of after asingle use, or they can be designed to be used multiple times. Versionsmay, in either or both cases, be reconditioned for reuse after at leastone use. Reconditioning may include any combination of the steps ofdisassembly of the device, followed by cleaning or replacement ofparticular pieces, and subsequent reassembly. In particular, someversions of the device may be disassembled, and any number of theparticular pieces or parts of the device may be selectively replaced orremoved in any combination. Upon cleaning and/or replacement ofparticular parts, some versions of the device may be reassembled forsubsequent use either at a reconditioning facility, or by an operatorimmediately prior to a procedure. Those skilled in the art willappreciate that reconditioning of a device may utilize a variety oftechniques for disassembly, cleaning/replacement, and reassembly. Use ofsuch techniques, and the resulting reconditioned device, are all withinthe scope of the present application.

By way of example only, versions described herein may be sterilizedbefore and/or after a procedure. In one sterilization technique, thedevice is placed in a closed and sealed container, such as a plastic orTYVEK bag. The container and device may then be placed in a field ofradiation that can penetrate the container, such as gamma radiation,x-rays, or high-energy electrons. The radiation may kill bacteria on thedevice and in the container. The sterilized device may then be stored inthe sterile container for later use. A device may also be sterilizedusing any other technique known in the art, including but not limited tobeta or gamma radiation, ethylene oxide, or steam.

Having shown and described various embodiments of the present invention,further adaptations of the methods and systems described herein may beaccomplished by appropriate modifications by one of ordinary skill inthe art without departing from the scope of the present invention.Several of such potential modifications have been mentioned, and otherswill be apparent to those skilled in the art. For instance, theexamples, embodiments, geometrics, materials, dimensions, ratios, steps,and the like discussed above are illustrative and are not required.Accordingly, the scope of the present invention should be considered interms of the following claims and is understood not to be limited to thedetails of structure and operation shown and described in thespecification and drawings.

1-20. (canceled)
 21. An apparatus, comprising: (a) a body; (b) a cannulaextending distally from the body, wherein the cannula is flexible,wherein the cannula is sized and configured to advance between a scleraand a choroid of a patient's eye; and (c) a needle slidably disposed inthe cannula, wherein the needle includes: (i) a sharp distal tip,wherein the needle is configured to translate relative to the cannulabetween a proximal position and a distal position, wherein the distaltip is configured to be positioned inside the cannula when the needle isin the proximal position and wherein the distal tip is configured to bepositioned outside the cannula when the needle is in the distalposition, (ii) a curved portion, wherein the needle is resilientlybiased to extend along a curve through the curved portion, and (iii) astraight distal portion extending along an exit axis, the straightdistal portion extending between the curved portion and the sharp distaltip, wherein the needle is resiliently biased to extend along a straightpath along the straight distal portion.
 22. The apparatus of claim 21,wherein the cannula includes an opening.
 23. The apparatus of claim 22,wherein the opening faces distally.
 24. The apparatus of claim 21,wherein the curved portion is resiliently biased to define a constantradius of curvature.
 25. The apparatus of claim 24, wherein the radiusof curvature is between approximately 7 mm and approximately 12 mm. 26.The apparatus of claim 24, wherein the radius of curvature is betweenapproximately 4 mm and approximately 15 mm.
 27. The apparatus of claim24, wherein the radius of curvature is between approximately 9 mm andapproximately 10 mm.
 28. The apparatus of claim 21, wherein the curvedportion is configured to position the distal tip at a progressivelyincreasing exit angle relative to a longitudinal axis of the cannulabased on a distance to which the needle is advanced distally relative tothe cannula.
 29. The apparatus of claim 21, wherein the curved portioncomprises a first curved region and a second curved region, wherein thefirst curved region is located near a distal portion of the needle andwherein the second curved region is located proximal to the first curvedregion.
 30. The apparatus of claim 21, wherein the needle furtherincludes a straight proximal portion, wherein the curved portion islongitudinally positioned between the straight proximal portion and thestraight distal portion.
 31. The apparatus of claim 21, wherein thecannula is flexible enough to conform to structures and contours of thepatient's eye yet the cannula has sufficient column strength to permitadvancement of the cannula between the sclera and the choroid of thepatient's eye without buckling.
 32. The apparatus of claim 21, whereinthe exit axis extends distally from the cannula at an exit angle ofapproximately 7 degrees to approximately 9 degrees relative to alongitudinal axis of the cannula, wherein the exit angle is configuredto deflect the needle in a direction to ensure penetration of the needleinto the choroid of the patient's eye and to minimize the possibility ofthe needle continuing beneath the choroid of the patient's eye through asuprachoroidal space of the patient's eye.
 33. An apparatus, comprising:(a) a body; (b) a cannula extending distally from the body, wherein thecannula is flexible, wherein the cannula is sized and configured toadvance between a sclera and a choroid of a patient's eye, wherein thecannula has a generally rectangular cross-sectional shape that isconfigured to prevent the cannula from rotating as the cannula isinserted into the patient's eye, wherein the cannula includes: (i)opposing inner and outer surfaces, (ii) a distal end, (iii) an opening,and (iv) a needle guide that is coupled with the inner surface of thecannula, wherein the needle guide is made from a different material fromthe cannula, wherein the needle guide does not extend into the opening;and (c) a needle slidably disposed in the cannula, wherein the generallyrectangular cross-sectional shape of the cannula is configured to ensurethat the needle exits from the opening of the cannula in a predictabledirection, wherein the needle is configured to extend through a lumen ofthe needle guide, wherein the needle includes: (i) a sharp distal tip,wherein the needle is configured to translate relative to the cannulabetween a proximal position and a distal position, wherein the distaltip is configured to be positioned inside the cannula when the needle isin the proximal position and wherein the distal tip is configured toextend past the opening when the needle is in the distal position, and(ii) a curved portion, wherein the curved portion is configured toprovide an oblique exit angle to a portion of the needle extending pastthe opening when the needle is in the distal position.
 34. The apparatusof claim 33, wherein the curved portion is resiliently biased to assumea curved configuration, wherein the curved portion is further configuredto deform to a substantially straight configuration within the cannulawhen the needle is in the proximal position.
 35. The apparatus of claim34, wherein the curved portion is resiliently biased to define a radiusof curvature, wherein the radius of curvature is between 9 mm and 11 mmwhen the curved portion is disposed outside of the cannula.
 36. Theapparatus of claim 33, wherein the opening is located between theopposing inner and outer surfaces, wherein the opening defines aperimeter that increases moving outwardly from the inner surface to theouter surface of the cannula which is configured to achieve a broaderrange of exit angles based on the extent to which the needle is advanceddistally.
 37. The apparatus of claim 33, wherein the needle is selectedfrom the group consisting of between 27 gauge and 45 gauge needles,wherein the size of the needle is configured to allow the needle topenetrate through the choroid of the patient's eye and to be removedsuch that the choroid of the patient's eye is self-sealing.
 38. Anapparatus, comprising: (a) a body; (b) a cannula extending distally fromthe body, wherein the cannula is flexible, wherein the cannula is sizedand configured to advance between a sclera and a choroid of a patient'seye; (c) a needle slidably disposed in the cannula, wherein the needleincludes: (i) a sharp distal tip, wherein the needle is configured totranslate relative to the cannula between a proximal position and adistal position, wherein the distal tip is configured to be positionedinside the cannula when the needle is in the proximal position andwherein the distal tip is configured to be positioned outside thecannula when the needle is in the distal position, and (ii) a curvedportion, wherein the needle is resiliently biased to extend along acurve through the curved portion, wherein the curved portion isresiliently biased to define a constant radius of curvature; and (d) anactuator configured to distally advance the needle relative to thecannula to position the needle at a predetermined location within thepatient's eye.
 39. The apparatus of claim 38, wherein the needle is astainless steel hypodermic needle that is sized and configured todeliver a therapeutic agent while being small enough to minimizeincidental trauma as the stainless steel hypodermic needle penetratestissue structures of the patient's eye.
 40. The apparatus of claim 38,wherein the cannula includes a distal end that is configured to provideseparation between the sclera and the choroid of the patient's eye toenable the cannula to be advanced between the sclera and the choroid ofthe patient's eye while not inflicting trauma to either the sclera orthe choroid of the patient's eye.